Reinfection rates after one- and two-stage revision surgery for hip and knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Revisions for periprosthetic joint infection of knee and hip arthroplasty can be performed following one- or two-stage treatment protocols. Current literature is inconclusive whether one protocol is superior to the other, as prior literature reported similar reinfection rates for both treatment options. We aimed to provide a systematic review and meta-analysis of current literature on septic arthroplasty revisions. METHODS: Between April 2015 and December 2020, Medline, Embase, and The Cochrane Library were searched for studies reporting reinfection outcomes in patients treated with one-stage and two-stage knee or hip revision arthroplasty. Two reviewers independently extracted data and disagreements were resolved by a third investigator. We utilized a double arcsine transformation, prior to pooling using a random-effects model. RESULTS: For hip revision arthroplasty, we identified 14 one-stage studies (n = 1237) with a pooled reinfection rate of 5.7% (95% CI 3.7-8.1%), and 46 two-stage studies (n = 5009) with a reinfection rate of 8.4% (95% CI 6.9-9.9%). For knee revision arthroplasty, 6 one-stage studies (n = 527) and 48 two-stage studies (n = 4344) were identified with reinfection rates of 12.7% (7.0-19.7%) and 16.2% (13.7-19.0%), respectively. Overall, reinfection rates did not vary substantially after subgroup analysis. Limitations of our study are the limited amount of one-stage studies that introduce a potential bias. CONCLUSION: The reinfection rates following one- and two-stage hip and knee arthroplasty revisions were similar. Knee reinfection rates have increased compared to the previous analysis. Individual patient characteristics and adequate treatment algorithms are needed for a more individual selection approach, until a randomized trial is performed.

Synovial-Based Tests Outperform Serum Markers to Rule Out Infection in Total Knee Arthroplasty and Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Total knee arthroplasty (TKA) provides successful results in most patients. Periprosthetic joint infection (PJI) accounts for up to 25% of failed TKAs needing revision. In clinical practice, consensus in diagnostic strategy for excluding or diagnosing PJI is still lacking. In this systematic review and meta-analysis, we aim to provide a simplified data-driven diagnostic strategy for aseptic knee and hip revision surgeons to rule out PJI in the outpatient clinic phase. METHODS: A literature search in EMBASE, MEDLINE, PubMed, and Cochrane was conducted. Studies involving the diagnosis of PJI in patients with failed TKAs and total hip arthroplasties needing revision were identified. Only studies using the Musculoskeletal Infection Society criteria were included. Quality was assessed using MINORS criteria. Meta-analysis was performed for each diagnostic test identified in the included studies. Pooled estimates of diagnostic accuracy measures were calculated using a bivariate model and plotted in summary receiver-operator characteristic curves. Positive and negative predictive values were calculated in a hypothetical sample of patients with a given disease prevalence. RESULTS: Twenty-four studies met the inclusion criteria, describing a total of 2974 patients. Quality scores ranged from 13 to 19. Meta-analysis could be performed on 7 unique diagnostic tests. Highest pooled sensitivity and specificity were demonstrated for α-defensin with values of 86% and 96.6%, respectively. α-defensin and white blood cell count in synovial fluid demonstrate highest negative predictive value values. CONCLUSIONS: We recommend, in a clinical setting with low-intermediate prevalence of PJI, performing arthrocentesis and joint fluid analysis using α-defensin and/or white blood cell count before revision TKA and revision total hip arthroplasty surgery to rule out PJI.

Giant Seromal Cyst Development After Tourniquet Use During Total Knee Arthroplasty: A Case Report.

CASE: An 84-year old woman developed 2 large seromal cysts at the medial side of her right thigh, 4 months after total knee arthroplasty (TKA). The cysts were located at the place where the tourniquet, during surgery, had been applied. The diagnosis was confirmed with echography and magnetic resonance imaging. Both cysts were resected, and the patient recovered completely, after one relapse in which a lymphatic vessel was sutured. CONCLUSION: Development of seromal cyst after tourniquet use during TKA is a rare but serious complication.

Identification of early prognostic factors for knee and hip arthroplasty; a long-term follow-up of the CHECK cohort.

BACKGROUND: Patients with the clinical symptoms of knee or hip osteoarthritis without solid X-ray features present a therapeutic dilemma. The question arises whether the decision for a surgical treatment should be based on the clinical presentation or the X-ray. OBJECTIVE: To determine prognostic patient factors for knee and hip arthroplasty when the X-ray does only show Kellgren and Lawrence grade 0-2 osteoarthritis. STUDY DESIGN: Nationwide prospective cohort study. METHODS: Participants of the Cohort Hip and Cohort Knee (CHECK) with KL 0-2 osteoarthritis on the X-ray were contacted to determine whether any knee or hip arthroplasty had taken place. A Cox proportional hazards regression analysis was performed to find baseline patient factors predicting the decision for arthroplasty. RESULTS: Regarding the knee, sex HR 0.207 P = 0.030, BMI HR 1.081 P = 0.018 and WOMAC total sum score HR 1.022 P = 0.017 were statistically significant predictors of the outcome arthroplasty. Age was not a significant predictor (P = 0.079). Concerning the hip, sex HR 2.103 P = 0.012, age HR 1.062 P = 0.022 and WOMAC total sum score HR 1.019 P = 0.029 were found to be statistically significant predictors for arthroplasty. BMI (P = 0.576), contralateral pain (P = 0.877) and health perception (P = 0.405) did not predict the end point hip arthroplasty. CONCLUSION: Predictors for knee arthroplasty were being female, having a higher BMI and a higher WOMAC total sum score. Predictors for hip arthroplasty were being male, having a higher age and a higher WOMAC total sum score. The incidence of arthroplasty was 5.1% (10.2 years) for the knee and 10.2% (9.7 years) for the hip.

Long-term Effect of Injection Treatment for Osteoarthritis in the Knee by Orthokin Autologous Conditioned Serum.

Background Orthokin is an intra-articular autologous conditioned serum (ACS). Its use might have a beneficial biological effect on pain and function of osteoarthritis in the knee. However, earlier studies lack any consensus on its clinical application and disease modifying effect. Objective The aim of this study was to investigate the long-term effect of Orthokin injection treatment on prevention of surgical treatment for end-stage knee osteoarthritis. Study Design Prospective cohort study. Methods Patients of the previously published Orthokin cohort were contacted to determine whether any intra-articular surgical intervention or osteotomy of the study knee had taken place during the past decade. A log-rank test was performed to evaluate the differences in the survival distribution for the 2 types of intervention: Orthokin versus placebo. Results The survival distributions for the 2 interventions were not statistically significantly different, χ2(1) = 2.069, P = 0.150. After 7.5 ± 3.9 years, 46.3% of the placebo and 40.3% of the Orthokin group had been treated surgically. Conclusion The use of Orthokin in knee osteoarthritis patients did not result in a delay regarding surgical treatment. Clinical Relevance The intra-articular use of Orthokin does not seem to prevent or delay surgical intervention at 10 years after treatment for end-stage knee osteoarthritis.

Chondrogenic potential of articular chondrocytes depends on their original location.

OBJECTIVE: This study aimed to investigate the regenerative capacity of chondrocytes derived from debrided defect cartilage and healthy cartilage from different regions in the joint to determine the best cell source for regenerative cartilage therapies. METHODS: Articular cartilage was obtained from Outerbridge grade III and IV cartilage lesions and from macroscopically healthy weight-bearing and nonweight-bearing (NWB) locations in the knee. Chondrocytes isolated from all locations were either pelleted directly (P0 pellets) or after expansion (P2 pellets) and analyzed for glycosaminoglycan (GAG), DNA, and cartilage-specific gene expression. Harvested cartilage samples and cultured pellets were also analyzed by Safranin O histology and immunohistochemistry for collagen I, II, and X. Immunohistochemical stainings were quantified using a computerized pixel-intensity staining segmentation method. RESULTS: After 4 weeks of culture, the P0 pellets derived from grade III or healthy weight-bearing chondrocytes contained more (p<0.015) GAG and GAG normalized per DNA compared to those from grade IV and NWB locations. After expansion, these differences were lost. Cartilage-specific gene expression was higher (p<0.04) in P0 pellets from grade III chondrocytes compared to grade IV chondrocytes. Semiquantitative immunohistochemistry showed a more intense (p<0.033) collagen I and X staining for grade IV debrided cartilage compared to grade III and weight-bearing cartilage. Also, collagen type X staining intensity was higher (p<0.033) in NWB cartilage compared to grade III and weight-bearing regions. CONCLUSION: Chondrocytes derived from debrided cartilage perform better than cells from the NWB biopsy site, however, this difference is lost upon expansion. Based thereon, the debrided defect cartilage could be a viable donor site for regenerative cartilage surgery.

Cell type and transfection reagent-dependent effects on viability, cell content, cell cycle and inflammation of RNAi in human primary mesenchymal cells.

The application of RNA interference (RNAi) has great therapeutic potential for degenerative diseases of cartilaginous tissues by means of fine tuning the phenotype of cells used for regeneration. However, possible non-specific effects of transfection per se might be relevant for future clinical application. In the current study, we selected two synthetic transfection reagents, a cationic lipid-based commercial reagent Lipofectamine RNAiMAX and polyethylenimine (PEI), and two naturally-derived transfection reagents, namely the polysaccharides chitosan (98% deacetylation) and hyaluronic acid (20% amidation), for siRNA delivery into primary mesenchymal cells including nucleus pulposus cells, articular chondrocytes and mesenchymal stem cells (MSCs). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an endogenous model gene to evaluate the extent of silencing by 20 nM or 200 nM siRNA at day 3 and day 6 post-transfection. In addition to silencing efficiency, non-specific effects such as cytotoxicity, change in DNA content and differentiation potential of cells were evaluated. Among the four transfection reagents, the commercial liposome-based agent was the most efficient reagent for siRNA delivery at 20 nM siRNA, followed by chitosan. Transfection using cationic liposomes, chitosan and PEI showed some decrease in viability and DNA content to varying degrees that was dependent on the siRNA dose and cell type evaluated, but independent of GAPDH knockdown. Some effects on DNA content were not accompanied by concomitant changes in viability. However, changes in expression of marker genes for cell cycle inhibition or progression, such as p21 and PCNA, could not explain the changes in DNA content. Interestingly, aspecific upregulation of GAPDH activity was found, which was limited to cartilaginous cells. In conclusion, non-specific effects should not be overlooked in the application of RNAi for mesenchymal cell transfection and may need to be overcome for its effective therapeutic application.

Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture.

BACKGROUND: Autologous chondrocyte implantation (ACI) is traditionally a 2-step procedure used to repair focal articular cartilage lesions. With use of a combination of chondrons (chondrocytes in their own territorial matrix) and mesenchymal stromal cells (MSCs), ACI could be innovated and performed in a single step, as sufficient cells would be available to fill the defect within a 1-step surgical procedure. Chondrons have been shown to have higher regenerative capacities than chondrocytes without such a pericellular matrix. PURPOSE: To evaluate cartilage formation by a combination of chondrons and MSCs in vitro and in both small and large animal models. STUDY DESIGN: Controlled laboratory study. METHODS: Chondrons and MSCs were cultured at different ratios in vitro containing 0%, 5%, 10%, 20%, 50%, or 100% chondrons (n = 3); embedded in injectable fibrin glue (Beriplast); and implanted subcutaneously in nude mice (n = 10; ratios of 0%, 5%, 10%, and 20% chondrons). Also, in a 1-step procedure, a combination of chondrons and MSCs was implanted in a freshly created focal articular cartilage lesion (10% chondrons) in goats (n = 8) and compared with microfracture. The effect of both treatments, after 6-month follow-up, was evaluated using biochemical glycosaminoglycan (GAG) and GAG/DNA analysis and scored using validated scoring systems for macroscopic and microscopic defect repairs. RESULTS: The addition of MSCs to chondron cultures enhanced cartilage-specific matrix production as reflected by a higher GAG production (P < .03), both in absolute levels and normalized to DNA content, compared with chondrocyte and 100% chondron cultures. Similar results were observed after 4 weeks of subcutaneous implantation in nude mice. Treatment of freshly created cartilage defects in goats using a combination of chondrons and MSCs in Beriplast resulted in better microscopic, macroscopic, and biochemical cartilage regeneration (P ≤ .02) compared with microfracture treatment. CONCLUSION: The combination of chondrons and MSCs increased cartilage matrix formation, and this combination of cells was safely applied in a goat model for focal cartilage lesions, outperforming microfracture. CLINICAL RELEVANCE: This study describes the bench-to-preclinical development of a new cell-based regenerative treatment for focal articular cartilage defects that outperforms microfracture in goats. In addition, it is a single-step procedure, thereby making the expensive cell expansion and reimplantation of dedifferentiated cells, as in ACI, redundant.

Articular cartilage evaluation after TruFit plug implantation analyzed by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

BACKGROUND: Quantitative MRI of articular cartilage has rapidly developed in recent years and provides the clinician with a noninvasive tool to determine the biological consequence of an intervention. PURPOSE: To evaluate the quality of intra-articular cartilage, using the dGEMRIC scanning technique, 1 year after TruFit implantation. The hypothesis was that implantation of a TruFit plug does not lead to damage at the opposing articular cartilage. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 13 patients (age, 32 ± 8 years) were evaluated with dGEMRIC at 12 ± 4 months after treatment of an osteochondral lesion by implantation of 1 or multiple TruFit plugs. The dGEMRIC scanning protocol was applied 90 minutes after intravenous Magnevist (0.2 mmol/kg body weight) injection. Different regions of interest (ROIs) were defined: the femur cartilage, cartilage directly surrounding the implanted TruFit plug, the TruFit plug, and the articulating and nonarticulating tibia cartilage. The average dGEMRIC index (T1gd; magnetic resonance imaging relaxation time per ROI) was calculated by a pixel-by-pixel curve fitting using the Levenberg-Marquardt method. Differences between the mean T1gd of the individual ROI for all patients were tested using analysis of variance with post hoc Bonferroni correction. A P value <.05 was considered statistically significant. RESULTS: The average T1gd of the TruFit ROI (385 ± 74 ms) was comparable with those in the femur (409 ± 49 ms) and surrounding (392 ± 64 ms) ROIs (P ≥ .339). The average T1gds for the articulating (578 ± 133 ms) and nonarticulating (516 ± 118 ms) ROIs were higher compared with the femur (409 ± 49 ms), surrounding (392 ± 64 ms), and TruFit (385 ± 74 ms) ROIs (P < .002), while no difference was observed between the tibia ROIs (P = .160). CONCLUSION: Implantation of the TruFit plug in osteochondral lesions does not damage the opposing or surrounding surface, and newly formed tissue inside the plug has cartilage-like dGEMRIC characteristics 12 months after implantation. The implantation of synthetic TruFit plugs is safe for the opposing cartilage, an item that is frequently discussed when using such materials to treat focal cartilage defects.

Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model.

INTRODUCTION: This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee. METHODS: IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogenous IL-6 and addition of IL-6, in a regeneration model and in osteoarthritic explants in the presence of synovial fluid, respectively. Readout parameters were DNA and glycosaminoglycan (GAG) content and release. Differences between controls and IL-6 blocked or supplemented samples were determined by univariate analysis of variance using a randomized block design. RESULTS: Synovial fluid of patients with symptomatic cartilage defects contained more IL-6 than synovial fluid of healthy donors (P = 0.001) and did not differ from osteoarthritic donors. IL-6 production of osteoarthritic chondrocytes during cartilage regeneration was higher than that of healthy and defect chondrocytes (P < 0.001). Adding IL-6 increased GAG production by healthy chondrocytes and decreased GAG release by osteoarthritic chondrocytes (P < 0.05). Inhibition of IL-6 present in osteoarthritic synovial fluid showed a trend towards decreased GAG content of the explants (P = 0.06). CONCLUSIONS: Our results support a modest anabolic role for IL-6 in cartilage matrix production. Targeting multiple cytokines, including IL-6, may be effective in improving cartilage repair in symptomatic cartilage defects and osteoarthritis.

Patient profiling in cartilage regeneration: prognostic factors determining success of treatment for cartilage defects.

BACKGROUND: Cartilage therapy for focal articular lesions has been implemented for more than a decade, and it is becoming increasingly available. What is still lacking, however, is analysis of patient characteristics to help improve outcome or select patients for specific treatment. PURPOSE: To analyze the prognostic value of patient age and defect size, age, and location on clinical outcome 3 years after cartilage therapy. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Fifty-five patients (age, 35 +/- 9 years) were randomly selected from a prospective database. Each had a traumatic knee injury, each was treated for a focal cartilage lesion, and each was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) 3 years after surgery. Patient characteristics (ie, patient age and defect size, age, and location) were tested for valid inclusion in the regression model. Multiple linear regression was used to determine which variables influenced clinical improvement. Binary KOOS scores were generated on the basis of age-matched healthy patients and assessed in a logistic regression analysis. RESULTS: Normality tests confirmed normal distribution for each variable (P < .05). Defect size did not influence clinical improvement (P > .05). Clinical outcome regarding the treatment of medial defects was better than that of the lateral defects (10.38-25.26 points for the different KOOS subscales; P < .05). The KOOS improvement from baseline was better for patients > or =30 years compared with patients > or =30 years (7.31-29.24 points for the different KOOS subscales; P < .05). Patients with defects <24 months were more likely to report the age-matched healthy reference KOOS (odds ratio, 1.8-4.0; P < .05). CONCLUSION: This study illustrates the influence of patient age and defect location and age on clinical outcome 3 years after treatment of a focal cartilage lesion in patients with a traumatic knee injury.

Treatment selection in articular cartilage lesions of the knee: a systematic review.

BACKGROUND: Several treatment options are available to repair articular cartilage lesions of the knee; however, evidence-based parameters for treatment selection are lacking. PURPOSE: To identify parameters for valid treatment selection in the repair of articular cartilage lesions of the knee. STUDY DESIGN: Systematic review. METHODS: A systematic search was conducted in the databases EMBASE, MEDLINE, and the Cochrane collaboration. The retrieved articles were screened for relevance on title and abstract followed by a full-text study quality appraisal of the remaining articles. Eventually, a total of 4 randomized controlled trials were included. RESULTS: Lesion size, activity level, and age were the influencing parameters for the outcome of articular cartilage repair surgery. Lesions greater than 2.5 cm(2) should be treated with sophisticated techniques, such as autologous chondrocyte implantation or osteochondral autologous transplantation, while microfracture is a good first-line treatment option for smaller (<2.5 cm(2)) lesions. Patients who are active show better results after autologous chondrocyte implantation or osteochondral autologous transplantation when compared with microfracture. Younger patients (<30 years) seem to benefit more from any form of cartilage repair surgery compared with those over 30 years of age. CONCLUSION: Lesion size, activity level, and patient age are factors that should be considered in selecting treatment of articular cartilage lesions of the knee. In addition, these factors are a step toward evidence-based, instead of surgeon-preferred, treatment of articular cartilage lesions of the knee.